Fos is required for EGF stimulation of the gastrin promoter

Gastrin gene expression is regulated by developmental cues, pH, and inflammation. These processes are mediated by various extracellular ligands, e.g., growth factors, cytokines, and neuropeptides that also stimulate c-fos gene expression. Therefore, to determine whether Fos is required for stimulation of the gastrin promoter, a c-fos sense expression vector was coexpressed with a gastrin reporter construct in a GH4 rat pituitary cell line. We found that epidermal growth factor (EGF) and tumor necrosis factor-alpha (TNF-alpha) transiently stimulate an increase in Fos protein that precedes stimulation of the gastrin promoter. However, the induction mediated by TNF-alpha was weaker than that mediated by EGF, indicating minimal overlap of the signaling pathways activated by EGF and TNF-alpha. Accordingly, overexpression of c-fos mRNA facilitated primarily EGF rather than TNF-alpha induction of the gastrin promoter. Expression of the c-fos gene in the absence of ligand did not stimulate the gastrin promoter. Thus c-fos gene expression is required but is not sufficient for induction of the gastrin promoter by EGF.